Piezoelectrically-activated antibacterial catheter for prevention of urinary tract infections in an on-demand manner

Abstract

Catheter-associated urinary tract infection (CAUTI) is a common clinical problem, especially during long-term catheterization, causing additional pain to patients. The development of novel antimicrobial coatings is needed to prolong the service life of catheters and reduce the incidence of CAUTIs. Herein, we designed an antimicrobial catheter coated with a piezoelectric zinc oxide nanoparticles (ZnO NPs)-incorporated polyvinylidene difluoride-hexafluoropropylene (ZnO-PVDF-HFP) membrane. ZnO-PVDF-HFP could be stably coated onto silicone catheters simply by a one-step solution film-forming method, very convenient for industrial production. In vitro, it was demonstrated that ZnO-PVDF-HFP coating could significantly inhibit bacterial growth and the formation of bacterial biofilm under ultrasound-mediated mechanical stimulation even after 4 weeks. Importantly, the on and off of antimicrobial activity as well as the strenth of antibacterial property could be controlled in an adaptive manner via ultrasound. In a rabbit model, the ZnO-PVDF-HFP-coated catheter significantly reduced the incidence CAUTIs compared with clinically-commonly used catheters under assistance of ultrasonication, and no side effect was detected. Collectively, the study provided a novel antibacterial catheter to prevent the occurrence of CAUTIs, whose antibacterial activity could be controlled in on-demand manner, adaptive to infection situation and promising in clinical application.

Keywords: Anti-infection; Nano-zinc oxide; Piezoelectricity; ROS; Uinary catheter.

Graphical abstract

Scheme 1

Schematic illustrating the preparation process and application of ZnO-PVDF-HFP antimicrobial coated catheters.

Fig. 1

Physical properties of piezoelectric antimicrobial ZnO-PVDF-HFP coated catheters. (A) Pattern maps, physical photographs and SEM images of catheter samples of Blank group, PVDF-HFP group, ZnO NPs group, and ZnO-PVDF-HFP group, (B) EDS results, (C) FTIR results, (D) PFM images, (E) Butterfly curves, (F) D₃₃ piezoelectricity coefficient results (G) Output voltages, (H) Short circuit currents, (I) Output charge. All statistics are expressed as mean ± standard deviation (* indicate statistical differences between PVDF-HFP-coated catheters and ZnO-PVDF-HFP-coated ones; *P < 0.001).

Fig. 2

In vitro antimicrobial effect of different groups of catheters against Escherichia coli and Staphylococcus aureus. (A) Colony counts in different groups, (B) Optical density values of E.coli, (C) Optical density values of S. aureus All statistics are expressed as mean ± standard deviation (* indicate statistical differences between different groups of catheters; *P < 0.05, **P < 0.01, ***P < 0.0001).

Fig. 3

In vitro antimicrobial effect of different groups of catheters. (A) Live/dead staining of E. coli, (B) Live/dead staining of S. aureus. (C) Bacterial death rate in different groups of E. coli. (D) Bacterial death rate in different groups of S. aureus. (E) SEM images of E. coli, (F) SEM images of S. aureus. All statistics are expressed as mean ± standard deviation (* indicate statistical differences between different groups of catheters; *P < 0.05, **P < 0.01, ***P < 0.001).

Fig. 4

Stability of ZnO-PVDF-HFP coating. (A) Comparison image of ZnO-PVDF-HFP coated catheter before and after bending, (B) SEM images of ZnO-PVDF-HFP coated catheter after 7, 14, and 28 days of immersion in artificial urine, (C) EDS results, (D) Output voltage, (E) Short-circuit current, (F) Output charge, (G) Optical density value of the immersed catheter after co-culturing with E. coli after co-culture with E. coli, (H) Optical density value of the bacterial fluid after co-culture of the immersed catheter with Staphylococcus aureus. All statistics are expressed as mean ± standard deviation (* indicate statistical differences between coated catheters soaked for different days and untreated catheters; *P < 0.0001).

Fig. 5

ROS production and biofilm resistance of different groups of catheters in E. coli and S. aureus. (A and B) ROS staining images of different groups of catheters in E. coli and S. aureus, (C and D) biofilm SEM images.

Fig. 6

In vitro biocompatibility and cytotoxicity of ZnO-PVDF-HFP coated catheters. (A) Live/dead stained images, (B) Percentage of live cells on the third day, (C) Cell viability of L929 cells cultured in extracts from ZnO-PVDF-HFP coated catheter. All data are expressed as mean ± standard deviation.

Fig. 7

In vivo antimicrobial effect of different groups of catheters. (A and B) Urine samples collected from animals for colony counting; (C) H&E staining of rabbit urethra; (D) H&E staining of rabbit bladder; (E and F) Immunohistochemical staining of IL-6 and TNF-α in rabbit urethra; (G and H) Immunohistochemical mean optical density values for IL-6 and TNF-α in rabbit urethra; (I and J) Immunohistochemical staining of IL-6 and TNF-α in rabbit bladder; (K and L) Immunohistochemical mean optical density values for IL-6 and TNF-α in rabbit bladder. All data are expressed as mean ± standard deviation (* indicate statistical differences between different groups of catheters; *P < 0.05,**P < 0.01,***P < 0.001,****P < 0.0001).